Effect of adenosine on heart rate variability in humans

Abstract

By stimulating afferent nerve endings in skeletal muscle, heart, kidney and the carotid body, adenosine infusion evokes a receptor-specific sympatho-excitatory reflex in humans that overrides its direct negative chronotropic effect. We tested the hypothesis that adenosine increases heart rate by suppressing parasympathetic and augmenting sympathetic components of heart rate variability. High-frequency (PH; 0.15-0.50 Hz) and low-frequency (PL; 0.05-0.15 Hz) components of heart rate variability total power (PT) were determined by spectral analysis. The ratios PH/PT and PL/PH respectively were used to estimate parasympathetic and sympathetic input to the sino-atrial node. Heart rate was recorded before and during a 5 min intravenous infusion of adenosine (140 micrograms.min-1.kg-1) in seven healthy men. Adenosine did not affect blood pressure, but increased heart rate by 33+/-6 beats/min, and reduced PT, PH, PL and PH/PT. In contrast, there was an increase in PL/PH. In a second experiment in nine men, brachial artery infusion of adenosine (15 micrograms.min-1.100 ml-1 forearm tissue) increased heart rate by 3 beats/min, had no effect on PT, PH, PL or PH/PT, yet increased PL/PH. Intra-arterial adenosine exerts a modest effect on heart rate by modulating cardiac sympathetic indices, without affecting parasympathetic indices, of heart rate variability, whereas intravenous infusion of adenosine reduces heart rate variability and raises heart rate by decreasing parasympathetic and increasing cardiac sympathetic tone. These reflex effects may become clinically relevant during adenosine stress testing, or when endogenous adenosine is increased, such as during ischaemia, exercise or vasodepressor reactions, or in heart failure.

Adenosine modulates oesophageal sensorimotor function in humans

“…The solution bags were enclosed in a dark, non-transparent, plastic bag, and the solution was infused over 30 min using a standard infusion pump. The adenosine dose was selected based on our pilot studies and others which showed that this dose does not cause chest tightness or discomfort, and is safe and well tolerated 34 43 44. Five minutes after starting the infusion, balloon distensions were repeated and the sensory and biomechanical properties of the oesophagus were re-assessed.…”

Effects of Adenosine Receptor Antagonists on Survival in Amitriptyline-poisoned Mice

“…Responses to the activation of the A 1 receptor include slowing of the heart rate and slowing of impulse conduction through the atrioventricular node, reduction of atrial contractility, inhibition of beta-adrenergic effects, and vasodilation (Bryan and Marshall, 1999). Activation of A 2 receptors causes vascular smooth muscle relaxation (Belardinelli et al, 1998;Rongen et al, 1999;Bryan and Marshall, 1999;Ngai et al, 2001;Hinschen et al, 2003), which can lead to a decrease in blood pressure. Subsequently, we showed that adenosine A 2a -receptor stimulation may be partly responsible for amitriptyline-induced vasodilation and hypotension in the rat model, since the adenosine A 1 antagonist, DPCPX, increased amitriptylineinduced vasodilation in the isolated aorta (Kalkan et al, 2004).…”

“…Adenosine, an endogenous nucleoside, elicits negative chronotropic and dromotropic effects (Dobson and Jones, 2004) and induces coronary vasodilation. The known cardiovascular effects of adenosine are mediated by the A 1 and A 2 (subtypes A 2a and A 2b ) receptors (Shryock and Belardinelli, 1997;Ralevic and Burnstock, 1998;Rongen et al, 1999). Responses to the activation of the A 1 receptor include slowing of the heart rate and slowing of impulse conduction through the atrioventricular node, reduction of atrial contractility, inhibition of beta-adrenergic effects, and vasodilation (Bryan and Marshall, 1999).…”

An alternative antidote therapy in amitriptyline-induced rat toxicity model: theophylline

“…The pharmacological effects of adenosine are related to specific G-proteins coupled to adenosine receptors. Adenosine A 1 receptor is coupled to its effector units (i.e., ionic channels and adenylyl cyclase) via guanine nucleotide-binding inhibitory protein G i (Rongen et al, 1999;Belardinelli et al, 1998). By affecting the G i proteins, adenylyl cyclase is inhibited, resulting in a decrease in cAMP concentrations.…”